Figure - available via license: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
Content may be subject to copyright.
N-linked and O-linked protein glycosylation occurs in the ER and Golgi apparatus. The synthesis of precursor glycans (mannose-rich glycans) begins on the cytosolic face of the ER and is completed after the glycans are flipped into the ER lumen and further branched by adding more units of mannose and glucose. ER-resident glycosyltransferases (GTs) transfer the precursor glycans to asparagine residues on nascent proteins to form N-linked precursor glycans. When the proteins are transported into the Golgi apparatus, the N-linked precursor glycans are edited by Golgi-resident glycosidases (GSs) and GTs to form mature and structurally-diverse N-linked glycans. O-linked protein glycosylation is mainly performed by Golgi-resident GTs.
Source publication
Post-translational modifications (PTMs) are known to be essential mechanisms used by eukaryotic cells to diversify their protein functions and dynamically coordinate their signaling networks. Defects in PTMs have been linked to numerous developmental disorders and human diseases, highlighting the importance of PTMs in maintaining normal cellular st...
Similar publications
Hair graying in mouse is attributed to the loss of melanocyte stem cell function and the progressive depletion of the follicular melanocyte population. Single gene, hair graying mouse models have pointed to a number of critical pathways involved in melanocyte stem cell biology, however, the broad range of phenotypic variation observed in human hair...
Helicobacter pylori infection is the main risk factor for gastric cancer. We characterized the interactions of H pylori with gastric epithelial progenitor and stem cells in humans and mice and investigated how these interactions contribute to H pylori-induced pathology.
We used quantitative confocal microscopy and 3-dimensional reconstruction of en...
As cell and molecular biology is becoming increasingly quantitative, there is an upsurge of interest in mechanistic modeling at different levels of resolution. Such models mostly concern kinetics and include gene and protein interactions as well as cell population dynamics. The final goal of these models is to provide experimental predictions, whic...
Background
Embryonic stem cells exist in inter-convertible sub-states leading to observed heterogeneity arising from seemingly homogeneous populations. Recently, it has been proposed that the stem cell compartment contains the ground state characterised by naïve pluripotency. Understanding molecular dynamics governing the transition from and towar...
Recent studies have demonstrated that breast milk contains a population of cells displaying many of the properties typical of stem cells. This review outlines progress made in this newly emerging field of stem cell biology and provides an analysis of the available data on purification, propagation and differentiation of certain types of progenitor...
Citations
... They modify the structure and properties of the protein in either a reversible or irrev ersible manner thr ough an array of biochemical r eactions and help them t o locat e themselves in the correct c ellular c ompartmen t. This regula t es the c ell's sig naling and phy siolog ical stat e [ 71 ]. Generally, PTMs are cat egorized into three types: cov alen t modifica tions of the side chains of amino acids of a protein, marked by the addition of chemical moieties to them; disulfide bond formation, a cov alen t bond formed bet ween t wo cy st eine residues b y remo val of tw o hy dr ogen atoms, pr oteolytic cleavage, marked by breaking peptide bonds [ 72 ]. ...
... 29 PTMs can be reversible or irreversible, and they change protein function in multiple ways, for example by altering substrate−enzyme interactions, subcellular localization or protein-protein interactions. 30,31 More than 400 biological PTMs have been discovered in both prokaryotic and eukaryotic cells. There are many more chemical artifact PTMs that occur during sample preparation, such as carbamylation. ...
... Proteins are possibly the main effectors of biological mechanisms [98]. Structural and functional modifications of proteins via various biochemical reactions such as post-translational modifications (PTMs) could lead to perturbations of the normal physiological and cellular processes, thus initiating the development as well as the progression of cancer [99,100]. Cancer-specific proteins possess the potential to perceive tumour microenvironment changes that can be exploited to discover valuable biomarkers [101]. ...
... Any aberrations [17] in these methylation and demethylation processes are linked to several diseases, including diabetes [12] and cancer [16] [18]. Thus, post-translational modi cations are an essential and critical area of scienti c investigation due to their signi cance in normal development [19] [20]and their correlation with various therapies [21]and translational oncology [22]. ...
Mutations are the driving force behind genetic variation, fueling both the oncogenesis and evolution of species. The mutation rate varies across the genome, potentially in response to chromatin organization by histone modifications and other factors. However, the exact relationship between the two is yet to be fully understood and requires further investigation. One modification involves the methylation of histone H3 at lysine 9, which creates heterochromatin and represses transcription in euchromatin to maintain genome stability for organism survival. This study aimed to determine the effect of H3K9 methylation alone, without other histone markers, on the mutation rate in fission yeast using fluctuation assays and statistical analysis. Our groundbreaking method has been proven to accurately estimate mutation rates of a single gene under two different conditions in a single experiment using one isogenic clone. Our research results demonstrate that the H3K9me markers increase the phenotypic mutation rate of the same gene. For prospective researchers, this study presents an innovative experimental approach that ensures unparalleled accuracy in gene analysis for genetics applications and epigenetic therapy.
... There are numerous kinds of posttranslational modifications (PTMs), including, but not limited to, serotonylation. PTMs are enzymatic and covalent modifications that occur by adding a modifying group like methyl, phosphoryl, or acetyl to one or more amino acids of the target protein, which alters said protein's characteristics [1]. They can be reversible or irreversible. ...
... They can be reversible or irreversible. Reversible processes include covalent events, while irreversible actions consist of proteolytic alterations and are often unidirectional [1,2]. These modifications are dynamic processes that allow for the regulation of function diversity and can alter the tertiary structure of the protein as well. ...
... However, the mechanisms regulating CTCF binding to chromatin are not fully understood [23][24][25] . PTMs are essential mechanisms to extend protein functions beyond what is dictated by gene transcription and to regulate cellular physiology 26,27 . Despite the potential diversity of CTCF PTMs 28-30 , only a few have been identified, such as acetylation, sumoylation, poly(ADP-ribosyl)nation, and phosphorylation 31-36 . ...
CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play a critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein to regulate numerous cellular processes. However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood. In this study, we uncovered the PTM profiling of CTCF and demonstrated that CTCF can be O-GlcNAcylated and arginine methylated. Functionally, we demonstrated that O-GlcNAcylation inhibits CTCF binding to chromatin. Meanwhile, deficiency of CTCF O-GlcNAcylation results in the disruption of loop domains and the alteration of chromatin loops associated with cellular development. Furthermore, the deficiency of CTCF O-GlcNAcylation increases the expression of developmental genes and negatively regulates maintenance and establishment of stem cell pluripotency. In conclusion, these results provide key insights into the role of PTMs for the 3D chromatin structure.
... This can limit the applicability of YSDs for studying proteins that require specific PTMs for their activity or binding properties. Researchers have explored alternative expression systems or engineered yeast strains to introduce specific PTM pathways, but this remains an ongoing challenge (Wang, et al., 2014). ...
Recombinant antibodies have emerged as powerful tools in various fields, including therapeutics, diagnostics, and research applications. The selection of high-affinity antibodies with desired specificity is a crucial step in the development of recombinant antibody-based products. In recent years, yeast surface display technology has gained significant attention as a robust and versatile platform for antibody selection. This graphical review provides an overview of the yeast surface display technology and its applications in recombinant antibody selection. We discuss the key components involved in the construction of yeast surface display libraries, including the antibody gene libraries, yeast host strains, and display vectors. Furthermore, we highlight the strategies employed for affinity maturation and optimization of recombinant antibodies using yeast surface display. Finally, we discuss the advantages and limitations of this technology compared to other antibody selection methods. Overall, yeast surface display technology offers a powerful and efficient approach for the selection of recombinant antibodies, enabling the rapid generation of high-affinity antibodies for various applications.
... Post-translational modifications (PTMs) play fundamental roles in protein function [18,19]. Aberrant methylation of oncoproteins and tumor suppressor proteins, which is dynamically regulated by methyltransferases and demethylases, plays a critical role in various human cancers [18]. ...
Androgen receptors (ARs) play key roles in prostate cancer (PCa) progression and castration-resistant prostate cancer (CRPC) resistance to drug therapy. SET and MYND domain containing protein 2 (SMYD2), a lysine methyltransferase, has been reported to promote tumors by transcriptionally methylating important oncogenes or tumor repressor genes. However, the role of SMYD2 in CRPC drug resistance remains unclear. In this study, we found that SMYD2 expression was significantly upregulated in PCa tissues and cell lines. High SMYD2 expression indicated poor CRPC-free survival and overall survival in patients. SMYD2 knockdown dramatically inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) potential of 22Rv1 and C4-2 cells. Conversely, ectopic overexpression of SMYD2 promoted these effects in 22Rv1 and C4-2 cells. Mechanistically, SMYD2 methylated and phosphorylated ARs to affect AR ubiquitination and proteasome degradation, which further alters the AR transcriptome in CRPC cells. Importantly, the SMYD2 inhibitor AZ505 had a synergistic therapeutic effect with enzalutamide in CRPC cells and mouse models; however, it could also re-sensitize resistant CRPC cells to enzalutamide. Our findings demonstrated that SMYD2 enhances the methylation and phosphorylation of ARs and affects AR ubiquitination and proteasome degradation to modulate CRPC cell resistance to enzalutamide, indicating that SMYD2 serves as a crucial oncogene in PCa and is an ideal therapeutic target for CRPC.
... This enables them to make more 36 informed decisions, develop targeted treatment plans, and ultimately improve patient 37 outcomes. In this review article, we briefly describe the methods used to generate high- 38 dimensional molecular data and then focus on the key role that machine learning plays in 39 the clinical application of such data. 40 The integration of machine learning with molecular data analysis holds great prom-41 ise for advancing precision medicine and transforming healthcare practices. ...
Advancements in genomic sequencing and mass spectrometry have revolutionized healthcare by providing a wealth of molecular data, enabling precise diagnoses and improved therapeutic approaches. Machine learning has emerged as a crucial tool for extracting meaningful insights from complex molecular datasets, empowering healthcare professionals to make informed decisions and develop targeted treatment plans. This review article highlights the pivotal role of machine learning in the clinical application of molecular data, emphasizing its potential to advance precision medicine and transform healthcare practices. The integration of AI and machine learning has the potential to enhance patient outcomes and improve healthcare delivery.
... The modifications in polymer molecules are termed as pre or post replicational , transcriptional or translational changes. Due to these modifications, the biopolymer got new functional or structural features thus allow them to perform more complicated functions in a well-organized manner [6][7][8][9][10] . ...
Post-transcriptional modifications of RNA play a key role in performing a variety of biological processes, such as stability and immune tolerance, RNA splicing, protein translation and RNA degradation. One of these RNA modifications is m5c which participates in various cellular functions like RNA structural stability and translation efficiency, got popularity among biologists. By applying biological experiments to detect RNA m5c methylation sites would require much more efforts, time and money. Most of the researchers are using pre-processed RNA sequences of 41 nucleotides where the methylated cytosine is in the center. Therefore, it is possible that some of the information around these motif may have lost. The conventional methods are unable to process the RNA sequence directly due to high dimensionality and thus need optimized techniques for better features extraction. To handle the above challenges the goal of this study is to employ an end-to-end, 1D CNN based model to classify and interpret m5c methylated data sites. Moreover, our aim is to analyze the sequence in its full length where the methylated cytosine may not be in the center. The evaluation of the proposed architecture showed a promising results by outperforming state-of-the-art techniques in terms of sensitivity and accuracy. Our model achieve 96.70% sensitivity and 96.21% accuracy for 41 nucleotides sequences while 96.10% accuracy for full length sequences.
